Forced Swimming Time Research Articles

Acupressure bladder meridian alleviates anxiety disorder via HMGB1

The aim of this study was to investigate the effects of acupressure bladder meridian (ABM) on anxiety in rats with chronic stress.Methods: The sugar water preference (SPF), tail suspension time (TST) and forced swimming time (FST) of rats were measured. The levels of reactive oxygen species (ROS), myeloperoxidase (MPO) in hippocampus tissue, oxidative stress parameters and inflammatory cytokines were detected. Underlying mechanisms of ABM on anxiety were detected. lipopolysaccharide (LPS) stimulated PC12 cells were adopted in vitro. HMGB1 knockdown were used in PC12 cells, and related signaling was further detected.Results: ABM significantly increased SPF, decreased TST and FST. ABM decreased ROS, MPO levels, decreased the levels of inflammatory cytokines. Furthermore, ABM decreased the levels of oxidative stress index. ABM reduced the expression of inflammation-related proteins mediated by HMGB1, increased nuclear factor erythroid2-related factor 2 (Nrf-2) and hemeoxygenase-1 (HO-1). In vitro PC12 cells, Rat serum (RS-ABM) treated with ABM significantly decreased LPS induced inflammation-related proteins and increased Nrf-2/HO-1 pathway. HMGB1 knockdown inhibited LPS-induced PC12 cell inflammatory signaling pathway and increased Nrf-2/HO-1 pathway.Conclusion: Our results demonstrated that ROS-dependent HMGB1 plays an important role in anxiety, and ABM exhibits inhibited inflammation in anxiety.

Xiegan-Liangxue-Jiedu Decoction Alleviated Psoriasis and Depressionlike Behavior in a Mouse Model: Role of the AC–cAMP–PKA–CREB Signaling Pathway

Objectives Psoriasis vulgaris is an immune-mediated inflammatory skin disease that is associated with depression. In this study, we investigated the effect of Xiegan–Liangxue–Jiedu (XGLXJD) decoction, a traditional Chinese medicine formula, on psoriasis based on network pharmacology, molecular docking, and animal experiments. Materials and Methods A protein–protein interaction (PPI) network was constructed using the overlapping targets of XGLXJD decoction and psoriasis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using Metascape database. High-performance liquid chromatography (HPLC) was used to investigate the main compounds of XGLXJD decoction. Molecular docking was performed to predict the potential interaction between the main compounds and proteins of interest. A C57 mouse model of psoriasis was established via continuous exposure to imiquimod. Seven days later, the XGLXJD decoction was orally administered at increasing doses for 6 days. The psoriasis area and severity index were calculated. Hematoxylin and eosin staining was used to examine skin morphology. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of adenylyl cyclase (AC), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α). Sucrose preference test and forced swimming test were used to assess depression-like behavior. Immunohistochemical (IHC) staining and immunofluorescence were used to investigate the cAMP-response element binding protein (CREB) signaling pathway. Results Overall, 162 overlapping targets were generated. A total of 398 biological processes, 84 molecular functions, and 47 cellular components were identified via GO analysis, whereas 140 pathways were identified via KEGG pathway analysis. The most notable signaling pathways were cAMP as well as downstream IL-17 and TNF-α signaling pathways. HPLC analysis revealed that the main compounds of XGLXJD decoction were paeoniflorin, isorhamnetin, quercetin, luteolin, kaempferol, and baicalein. The molecular docking assay indicated that the docking energies of the main compounds of XGLXJD decoction to the top hub genes were less than −5 kcal/mol. ELISA revealed that the administration of XGLXJD decoction decreased the levels of pro-inflammatory cytokines (TNF-α and IL-17). Furthermore, the AC, cAMP, and PKA levels were enhanced after its administration. IHC staining demonstrated that the administration of XGLXJD decoction activated the AC–cAMP–PKA–CREB signaling pathway in skin. In addition, it enhanced sucrose preference and forced swimming time percentage. It also enhanced the expression of cAMP and PKA in the hippocampus. Conclusion XGLXJD decoction alleviated psoriasis and depression-like behavior. The AC–cAMP–PKA–CREB signaling pathway may play a crucial role in mediating this effect.

Anti-fatigue activities of γ-aminobutyric acid-enriched soymilk in an acute exercise-treated mouse model via regulating AMPK/PGC-1α pathway

Gamma-aminobutyric acid (GABA), a four carbon non-protein amino acid, is extensively distributed in nature and shows various biological functions. In the present study, Lactobacillus brevis ATCC 367 and Lactobacillus plantarum ASCC 276, two producers with high GABA production capacity, were selected to ferment soymilk and their optimal culture conditions were investigated. Then, the anti-fatigue ability of GABA-enriched soy protein isolate (SPI) fermented milk was assessed by the weight-loaded forced swimming test and the related biochemical parameters were recorded to find possible reasons. Results demonstrated that soymilk added with glucose was capable of yielding the highest GABA content when used Streptococcus thermophilus 1303 and Lactobacillus brevis ATCC 367 as starter bacteria, and exhibited the high anti-fatigue effect in mice, mainly manifested in extending the forced swimming time, suppressing the blood lactic acid, urea nitrogen and lactate dehydrogenase content, and promoting the level of liver glycogen, muscle glycogen and muscle ATP. More importantly, SPI fermented milk beverages decreased reactive oxygen species levels via improving the concentrations of superoxide dismutase and glutathione peroxidase and inhibiting the content of malondialdehyd and promoted energy reserves by stimulating the expression of AMPK and PGC-1α in muscle, thus showing its fatigue-alleviating effect. Our study disclosed that there was a positive correlation between GABA content and anti-fatigue-related indicators of SPI fermented milk, which will be of interest for developing fermented milk with high anti-fatigue activity.

Aerobic Exercise Improves Depressive-like Behavior in CUMS-Induced Rats via the SIRT3/ROS/NLRP3 Signaling Pathway.

This study aimed to investigate the effect of exercise on depressive-like behavior induced by chronic unpredictable mild stress (CUMS) in rats and to explore the role of the SIRT3/ROS/NLRP3 signaling pathway in this process. Twenty-nine male 8-week-old Sprague Dawley rats were divided into a control group (CON) (nine rats) and a model group (twenty rats). Thirteen chronic stress stimuli were randomly applied once or twice per day for 35 days to induce depression in the model group rats. After the model was established, the model group rats were randomly divided into the CUMS group (CUMS) and the aerobic exercise + CUMS group (EX + CUMS). The EX + CUMS group received 8 weeks of aerobic exercise intervention for 6 days per week. Behavioral assessments were performed using the sucrose preference test and forced swimming test. The expression of SIRT3, NLRP3, IL-1β, and IL-18 in the hippocampus was detected using RT-PCR. The ROS level in the hippocampus was detected using immunofluorescence. The protein levels of SIRT3 and NLRP3 in the hippocampus were detected using western blotting. The protein levels of IL-1β and IL-18 in the hippocampus were measured using ELISA. After 5 weeks of chronic stress stimuli, the hippocampal function of rats in the CUMS model group was impaired, and their sucrose preference was reduced, while their forced swimming time was prolonged. The expression of SIRT3 decreased, ROS increased, and the expression of NLRP3 and the levels of IL-1β and IL-18 increased. Aerobic exercise increased the sucrose preference of rats, shortened their immobility time, increased the expression of SIRT3, and reduced the levels of ROS, NLRP3, IL-1β, and IL-18. Exercise can improve the depressive behavior of CUMS model rats, and its mechanism may be related to the upregulation of SIRT3 in the hippocampus, which plays an anti-inflammatory role.

Anti-Fatigue Effect of Viola odorata L. in Forced Swimming Test in Rat

Fatigue is a complex phenomenon that is explained as difficulty starting or keeping voluntary physical or mental activity leading to negative impacts on life and work performance. This study aimed to investigate the anti-fatigue effects of Viola odorata L. in an animal model. Aqueous and ethanol extracts of V. odorata were prepared and total phenolics content was determined. Then, the anti-fatigue activity of the extracts was evaluated via a weight-loaded forced swimming test in the rat. To this end, 48 male Wistar rats were randomly classified into 6 groups. The control group using distilled water and other groups with ethanol (EVO; 50, 100, 200 mg/kg) and aqueous extracts of V. odorata (WVO; 50, 100mg/kg) were gavaged once daily for four weeks. Then, the forced swimming was conducted and swimming time, as a fatigue factor was measured. In addition, to validate the effect of V. odorata on the endurance capacity of the rats, biochemical factors including glucose, lactate dehydrogenase (LDH), and tumor necrosis factor (TNF-α) were examined in the serum. Hepatotoxicity was also assessed using hematoxylin-eosin staining. Our data indicated that the forced swimming time of the EVO-100, EVO-200, and WVO-100 groups was significantly increased. The serum glucose in the group which received EVO-200 was increased significantly; while serum LDH levels in all treated groups were significantly decreased. Also, the serum level of TNF-α in the groups which received EVO-100 or 200 was increased significantly. However, there was no considerable difference in serum TNF-α level and no hepatotoxicity within aqueous extract groups. Pathology results showed fewer effects of the aqueous extract rather than ethanol extract on the liver. The results provide evidence for the development and use of V. odorata aqueous extract as an anti-fatigue supplement.

Structure, anti-fatigue activity and regulation on gut microflora in vivo of ethanol-fractional polysaccharides from Dendrobium officinale

This study was to investigate the antifatigue, prebiotic effects and their relationships to the structure properties of three ethanol precipitated polysaccharides from Dendrobium officinale (EPDO), as EPDO-40, EPDO-60 and EPDO-80. EPDOs with anti-fatigue activity were screened out by forced swimming test, and blood lactic acid (BLA), blood urea nitrogen (BUN), superoxide dismutase (SOD), liver glycogen, muscle glycogen, and intestinal microflora were investigated. Results showed that purified EPDO-60, 277.3 kDa, with a backbone consisted of 4-Manp and 4-Glcp. EPDO-60 had the best anti-fatigue activity, because it could significantly prolong the forced swimming time, as well as down-regulating the levels of BLA and BUN, increasing SOD. Proportions of Bacteroidetes and Firmicutes and abundance of Lactobacillus and Bifidobacterium in gut microflora increased after treated with EPDO-60. Accordingly, EPDO-60 could affect the community structure of gut microflora, leading to promote the balance of oxidation and antioxidation, and accelerated the fatigue metabolism in vivo.

Structure and potential anti-fatigue mechanism of polysaccharides from Bupleurum chinense DC

Two polysaccharides, BCP-1 and BCP-2, were obtained from Bupleurum chinense DC. by water extraction and ultrafiltration. BCP-1 (1.04 × 105 Da) and BCP-2 (2.14 × 104 Da) were composed of Mannose, Rhamnose, Glucose, Galactose, Arabinose, and Galacturonic acid in different proportions. They both contained oligogalacturonides in their main chain. Besides, the backbone of BCP-1 was composed of 4-β-Galp and 4,6-β-Glcp, and branched at C4 of 4,6-β-Glcp. While BCP-2 contained a backbone of 3,5-α-Araf residues with branches at C3. BCP-2 effectively extended the forced swimming time, improved the glycogen reserves and antioxidant system, decreased the levels of blood urea nitrogen, lactic acid, lactate dehydrogenase and creatinine kinase expression. It alleviated physical fatigue through regulating 5’-AMP-activated protein kinase (AMPK) and Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) signalling pathway in skeletal muscles. This study demonstrated that BCP-2 exhibited more effective anti-fatigue activity than BCP-1 potentially associated with its primary and higher structures.

Massage of Bladder Meridian Relieved Anxiety Induced by Chronic Stress in Rats.

The aim of this paper was to explore the mechanism of bladder meridian massage (BMM) on anxiety in rats with chronic stress. Chronic stress induced rats to establish rat anxiety model. The sugar water preference (SPF), tail suspension time (TST), and forced swimming time (FST) of rats were measured. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines in serum and hippocampus of rats were detected. Brain neurotransmitters (dopamine (DA), 5- hydroxytryptamine (5-HT), and norepinephrine (NE)) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Immunohistochemistry and western blotting were used to detect autophagy protein expression in hippocampus of rats. BMM significantly increased SPF, decreased TST and FST, increased SOD level in serum and hippocampus, and decreased MDA level and cytokine level. BMM reversed the changes of neurotransmitters. At the same time, BMM significantly decreased autophagy protein expression in hippocampus of rats. The above results show that BMM significantly relieve anxiety induced by chronic stress in rats.

Spore Powder of Paecilomyces hepiali Shapes Gut Microbiota to Relieve Exercise-Induced Fatigue in Mice.

Paecilomyces hepiali, a fungal strain isolated from natural Ophiocordyceps sinensis, contains similar pharmacologically active components, has been used widely as a substitute of O. sinensis in functional food and medicine. However, the components and anti-fatigue effects of P.hepiali spores and their mechanisms of action are largely unknown. Here, we compared the chemical composition in P.hepiali spore (HPS) and mycelium (HPM) by liquid chromatography with tandem mass spectrometry analysis. We found 85 metabolites with significant differences, and HPS contains more L-Malic acid, Oxalacetic acid, Fructose-1,6-bisphosphate, and L-Arginine than HPM. Then we evaluated their anti-fatigue effects and regulatory effects on the gut microbiota in mice. The forced swimming time (SW) was only significantly increased in HPS groups: the high and low dose of the HPS group was 101% and 72% longer than the control group, respectively. Both HPS and HPM treatment decreased lactic acid, blood urea nitrogen, creatine kinase while increased lactate dehydrogenase (LDH) levels in the blood. Moreover, mice treated with HPS and HPM showed less skeletal muscle fiber spacing and breakage. The relative abundance of Alistips, Eubacterium, Bacterium, Parasutterella, and Olsenella in the gut microbiota of the HPS group was higher than that in the HPM group through 16S rRNA gene sequencing analysis. These changes may be related to the regulation of nucleotide, amino acid, and carbohydrate metabolism. Correlation analysis between the gut microbiota and fatigue-related indicators suggested that Alistips, Clostridium, Akkermansia, Olsenella, and Lactobacillus were positively correlated with the SW and LDH content. Our findings demonstrated that HPS has beneficial anti-fatigue effects by regulating gut microbiota.

Highly Efficient Biotransformation of Notoginsenoside R1 into Ginsenoside Rg1 by Dictyoglomus thermophilum β-xylosidase Xln-DT.

Notoginsenoside R1 and ginsenoside Rg1 are the main active ingredients of Panax notoginseng, exhibiting anti-fatigue, anti-tumor, anti-inflammatory, and other activities. In a previous study, a GH39 β-xylosidase Xln-DT was responsible for the bioconversion of saponin, a natural active substance with a xylose group, with high selectivity for cleaving the outer xylose moiety of notoginsenoside R1 at the C-6 position, producing ginsenoside Rg1 with potent anti-fatigue activity. The optimal bioconversion temperature, pH, and enzyme dosage were obtained by optimizing the transformation conditions. Under optimal conditions (pH 6.0, 75°C, enzyme dosage 1.0 U/ml), 1.0 g/l of notoginsenoside R1 was converted into 0.86 g/l of ginsenoside Rg1 within 30 min, with a molar conversion rate of approximately 100%. Furthermore, the in vivo anti-fatigue activity of notoginsenoside R1 and ginsenoside Rg1 were compared using a suitable rat model. Compared with the control group, the forced swimming time to exhaustion was prolonged in mice by 17.3% in the Rg1 high group (20 mg/kg·d). Additionally, the levels of hepatic glycogen (69.9-83.3% increase) and muscle glycogen (36.9-93.6% increase) were increased. In the Rg1 group, hemoglobin levels were also distinctly increased by treatment concentrations. Our findings indicate that treatment with ginsenoside Rg1 enhances the anti-fatigue effects. In this study, we reveal a GH39 β-xylosidase displaying excellent hydrolytic activity to produce ginsenoside Rg1 in the pharmaceutical and food industries.

Olfactory Stimulation with Volatile Aroma Compounds of Basil (Ocimum basilicum L.) Essential Oil and Linalool Ameliorates White Fat Accumulation and Dyslipidemia in Chronically Stressed Rats.

We explored the physiological effects of inhaling basil essential oil (BEO) and/or linalool and identified odor-active aroma compounds in BEO using gas chromatography/mass spectrometry (GC–MS) and GC–olfactometry (GC–O). Linalool was identified as the major volatile compound in BEO. Three groups of rats were administered BEO and linalool via inhalation, while rats in the control group were not. Inhalation of BEO for 20 min only reduced the total weight gain (190.67 ± 2.52 g) and increased the forced swimming time (47.33 ± 14.84 s) compared with the control group (219.67 ± 2.08 g, 8.33 ± 5.13 s). Inhalation of BEO for 5 min (392 ± 21 beats/min) only reduced the pulse compared with the control group (420 ± 19 beats/min). Inhalation of linalool only reduced the weight of white adipose tissue (5.75 ± 0.61 g). The levels of stress-related hormones were not significantly different among the groups. The total cholesterol and triglyceride levels decreased after inhalation of BEO for 20 min (by more than −10% and −15%, respectively). Low-density lipoprotein cholesterol levels were lowered (by more than −10%) by the inhalation of BEO and linalool, regardless of the inhalation time. In particular, BEO inhalation for 20 min was associated with the lowest level of low-density lipoprotein cholesterol (53.94 ± 2.72 mg/dL). High-density lipoprotein cholesterol levels increased after inhalation of BEO (by more than +15%). The atherogenic index and cardiac risk factors were suppressed by BEO inhalation. Animals exposed to BEO and linalool had no significant differences in hepatotoxicity. These data suggest that the inhalation of BEO and linalool may ameliorate cardiovascular and lipid dysfunctions. These effects should be explored further for clinical applications.

Anti-fatigue activity of the polysaccharides isolated from Ribes stenocarpum Maxim

In the present study, the crude polysaccharides from Ribes stenocarpum Maxim. (RPs) were isolated by ultrasonic-assisted extraction. The physicochemical analysis revealed that RPs is a pyranose configuration connected by β-glycosidic bonds without three-stranded helical conformation, and is composed of mannose, ribose, glucuronic acid, galactose, glucose, arabinose, galacturonic acid, and xylose with a molecular weight of 44,200 Da. Furthermore, the animal experimental results demonstrated that RPs could significantly prolong the forced swimming time of mice, increase the liver glycogen and muscle glycogen levels, up-regulate the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in mice, and reduce the blood urea nitrogen (BUN), lactic acid (LD), and malondialdehyde (MDA) contents. The above results suggested that RPs could effectively reduce the oxidative stress response of mice during strenuous exercise and exert significant anti-fatigue activity.

Fermented Antler Recovers Stamina, Muscle Strength and Muscle Mass in Middle-Aged Mice

In a previous study, we found that Lactobacillus curvatus HY7602-fermented antler (FA) improved exercise endurance by increasement of muscle mass and strength in a young mouse model. In this study, we investigated the effect of FA on recovery of muscle mass and strength in aging-induced muscle loss. We have used a middle-aged model in which muscle decline begins in many mammalian species. All mice performed treadmill exercise and forced swimming, and measured muscle grip strength. Then, calf muscle weight and histological analysis, blood biomarker and gene expression in soleus muscle tissue were measured. Muscle strength and forced swimming time were significantly increased in the FA-intake groups compared to controls. The levels of muscle and liver damage-related indicators (ATL, ALP, LDH and CK) and muscle endurance, fatigue and exercise performance-related indicators (lactate and creatinine) were significantly improved by FA supplementation. In addition, FA regulates genes related to muscle protein degradation (Atrogin-1 and MuRF1) and muscle fiber synthesis (MyoD and Myf5), resulting in increased muscle mass, and fiber diameter and area values. The Bax/Bcl-2 ratio, related to apoptosis in skeletal muscle was significantly decreased. These results demonstrate that FA improves exercise performance with ameliorating blood biomarkers and also increases muscle mass and muscle strength by inhibiting muscle proteolysis and promoting muscle synthesis in a middle-aged mouse.

Anti-fatigue effects of fermented soybean protein peptides in mice.

Bioactive protein hydrolysates and peptides are believed to help counteract and ameliorate physical fatigue. Fermented soybean protein peptides (FSPPs) were prepared by protease hydrolysis and microbial fermentation. The present study aimed to evaluate the anti-fatigue properties of FSPPs. The forced swimming time in the FSPP group was 35.78% longer than the control group, the oxygen-resistant survival time of the FSPP group was significantly prolonged and the prolongation rate was 31.00%. In addition, FSPPs decreased the lactic acid (LD), blood urea nitrogen (BUN) and creatine kinase (CK) concentration by 27.47%, 25.93% and 21.70%, respectively, after treatment, while increasing the levels of liver glycogen and muscle glycogen by 93.35% and 67.31%, respectively. FSPPs can significantly increase gut microbiota diversity and regulate the species richness of gut microbiota. The results of real-time polymerase chain reaction (RT-PCR) and western blotting showed that FSPPs activate p-AMPK/PGC1-α and PI3K/Akt/mTOR signaling pathways. These results indicate that treatment with FSPPs induces anti-fatigue effects, which may be due to the mediating muscle protein synthesis and participation in skeletal muscle hypertrophy, providing energy for muscle cells. FSPPs may have potential applications in the food industry as functional material additives. © 2021 Society of Chemical Industry.

Synergistic effect of combined oyster peptide and ginseng extracts on anti-exercise-fatigue and promotion of sexual interest activity in male ICR mice

• Novelty, a synergistic effect of OPGE on anti-fatigue and sexual ability was explored. • OPGE promoted physical recovery and accelerated fatigue elimination. • OPGE increased sexual behavior of male mice after exhausted swimming. • OPGE enhanced the expression of testosterone synthesis related protease. Traditionally, ginseng and oyster are regarded as biological tonics for enhancing vital energy. In this study, a post-exercise fatigue model and copulatory test were performed to evaluate the effects of combined oyster peptide and ginseng extracts (OPGE) on anti-fatigue and sexual function. The forced swimming time of mice was prolonged by taking OPGE. Moreover, the level of serum lactic acid, blood urea nitrogen, and lactate dehydrogenase activity were decreased, while the liver glycogen content and antioxidant ability in skeletal muscles were increased. Furthermore, OPGE statistically improved the sexual behavioral indexes of exercise-fatigue mice. The levels of testosterone and follicle-stimulating hormone in serum, and the expression of testosterone synthesis-related-protease in testis were increased by OPGE administration, while phosphodiesterase-5 content was decreased. Overall, our study suggested that OPGE could be a potential androgen-like dietary supplement to accelerate the elimination of fatigue and improve testosterone-deficiency symptom after intensive training.

Taurine and Camel Milk Modulate Neurobehavioral and Biochemical Changes in Aluminum Chloride-Induced Alzheimer's Disease in Rats.

Alzheimer's disease (AD) is a neurodegenerative disease associated with deficiency in motor coordination, cognitive impairment, and excessive reactive oxygen species production in the brain. The study evaluated effects of taurine and camel milk (CM) on neurobehavior, amyloid-beta peptide 1-42 (Aβ) expression, acetylcholinesterase, and superoxide dismutase activities in aluminum chloride (AlCl3) model of Alzheimer's disease in rats. Thirty-five female Wistar rats were divided into seven groups (n = 5): Normal saline (0.2 mL/kg body weight); AlCl3 (100 mg/kg) (AD); CM (33 mL/kg); Taurine (50 mg/kg); AlCl3 (100 mg/kg) + CM (33 mL/kg); AlCl3 (100 mg/kg) + Taurine (50 mg/kg); and AlCl3 (100 mg/kg) + CM (33 mL/kg) + Taurine (50 mg/kg). The administration lasted for eight weeks via oral gavage. After the eighth week, neurobehavior assessments were performed. Rats were sacrificed, and brain and blood samples collected for analysis. There was a significant (p < 0.0001) increase in the duration of motor endurance in AD + CM rats, compared to AD rats. Duration of forced swimming time was lowest (p < 0.0001) in AlCl3 + Taurine rats, compared to that of AD rats. Concentration of Aβ peptide decreased (p < 0.05) in AD rats, treated with CM and/or combination. In taurine-treated rats, superoxide dismutase activity was significantly (p < 0.05) higher than in AD rats. Treatment with taurine + CM increased (p < 0.05) acetylcholinesterase activity compared to controls. Taurine and CM enhanced cognition and sensorimotor activity by decreasing Aβ peptide concentration and increasing superoxide dismutase and acetylcholinesterase activities in AD rats.

An overview of the behavioral, neurobiological and morphological effects of topiramate in rats exposed to chronic unpredictable mild stress

The environmental psychological stress causes depressive disorders. Stress causes many neurobiological, neurodegenerative changes in brain. Topiramate (TPM) is used in the treatment of epilepsy and psychiatric diseases. However, there are conflicting findings that TPM disrupts cognitive functions. We aimed to investigate the effects of TPM on depression, anxiety, learning and memory as well as neurobiological, morphological changes in rats exposed to chronic unpredictable mild stress (CUMS). After CUMS was formed by random application of nine mild stressors for 45 days, TPM (at doses of 0.1, 1, 10, 100 mg/kg) was administered for 21 days. Sucrose preference, locomotor activity, forced swimming, elevated plus maze and Morris water maze tests were performed. Corticosterone, BDNF (Brain-derived neurotrophic factor) and glutamate levels and volumes of hippocampus were evaluated. Body weights of the rats were measured. Immobilization time increased in CUMS, CUMS + TPM0.1 in forced swimming test and time spent in platform quadrant increased in Control + TPM1, CUMS, CUMS + TPM0.1, CUMS + TPM1 in Morris water maze test. Control + TPM1 decreased distance to platform in Morris water maze while CUMS + TPM100 increased. Learning is impaired in CUMS + TPM100 while it is improved in Control + TPM1. BDNF levels increased in CUMS and glutamate levels increased in CUMS, CUMS + TPM10. Body weight decreased in CUMS, CUMS + TPM0.1, CUMS + TPM1, CUMS + TPM100. Hippocampus volumes increased in CUMS. In conclusion, CUMS improved cognition and this finding was supported by the increase of BDNF levels and volume of hippocampus. TPM 1 mg/kg improved cognition in non-stressed rats. TPM 0.1 and 1 mg/kg improved while TPM 100 mg/kg impaired memory in rats exposed to stress.

Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice.

Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is one of the most refractory diseases in humans and is characterized by severe central fatigue accompanied with various symptoms that affect daily life, such as impaired memory, depression, and somatic pain. However, the etiology and pathophysiological mechanisms of CFS remain unknown. To investigate the pathophysiological role of transforming growth factor (TGF)-β1, we injected a cytokine into the lateral ventricle of a C57BL/6 mouse. The intracranial injection of TGF-β1 increased the immobility duration in a forced swimming test (FST) and time spent at the closed arm in elevated plus maze (EPM) analysis. The mice injected with TGF-β1 into their brain showed increased sensitivity to pain in a von Frey test, and had a decreased retention time on rotarod and latency time in a bright box in a passive avoidance test. In addition, the serum levels of muscle fatigue biomarkers, lactate dehydrogenase (LDH) and creatine kinase (CK), were significantly increased after administration of TGF-β1. Intracranial injection of TGF-β1 significantly reduced the production of tyrosine hydroxylase (TH) in the ventral tegmental area, accompanied by a decreased level of dopamine in the striatum. The suppression of TH expression by TGF-β1 was confirmed in the human neuroblastoma cell line, SH-SY5Y. These results, which show that TGF-β1 induced fatigue-like behaviors by suppressing dopamine production, suggest that TGF-β1 plays a critical role in the development of central fatigue and is, therefore, a potential therapeutic target of the disease.

Improvement of testosterone deficiency by fermented Momordica charantia extracts in aging male rats.

The online version contains supplementary material available at 10.1007/s10068-020-00872-x.

Jianpi Yiqi Shexue ameliorates immune thrombocytopenia related fatigue by regulating mitochondrial function

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease characterized by platelet destruction. In previous studies, Jianpi Yiqi Shexue (JPYQSX) was shown to increase the peripheral platelet (PLT) counts in patients with ITP. In addition, JPYQSX also dramatically alleviated weakness and fatigue. This study aimed to investigate the effect of JPYQSX on ITP related fatigue and to illuminate the underlying mechanisms of its therapeutic effects. Prednisone and different doses of JPYQSX were orally administered to mice with ITP. Post-treatment, all mice were subjected to a forced swimming test. In addition, blood samples were analyzed using an automated hematology analyzer. Spleen, liver, lungs, heart, kidneys, and colon tissues were collected to determine the expressions of reactive oxygen species (ROS), adenosine triphosphate (ATP), mitochondrial DNA (mtDNA), succinate dehydrogenase complex flavoprotein subunit A (SDHA), caseinolytic mitochondrial matrix peptidase proteolytic subunit (ClpP), and Lon peptidase 1 (Lonp1). Compared with the vehicle group, JPYQSX prolonged the forced swimming time, increased the PLT counts, and reduced the liver and spleen indices {calculated as follows: organ index (%) = [organ weight (mg)/body weight (g)] ×100%}. In addition, the levels of ROS were upregulated, while the ATP and mtDNA contents were downregulated in ITP model mice. Administration of JPYQSX restored the expression of these mitochondrial molecules to normal levels. Furthermore, JPYQSX also decreased the expressions of SDHA, ClpP, and Lonp1, which are closely related to mitochondrial activity. These findings suggest that JPYQSX prevents antiplatelet sera-mediated platelet destruction in ITP mice and ameliorates fatigue possibly through its effect on mitochondrial function. This study revealed JPYQSX as a potential alternative approach for ITP therapy.